RecruitingPhase 3NCT05849779

Inhaled Sevoflurane for ARDS Prevention

Randomized Clinical Trial of Inhaled Sedation With Sevoflurane in Critically Ill Patients at Risk of Developing the Acute Respiratory Distress Syndrome


Sponsor

University Hospital, Clermont-Ferrand

Enrollment

80 participants

Start Date

Jul 24, 2023

Study Type

INTERVENTIONAL

Conditions

Summary

This study focuses on patients who are at risk of developing a serious, life-threatening respiratory disease called Acute Respiratory Distress Syndrome (ARDS), which severely disrupts the function of their lungs. Preclinical studies have shown that the use of a volatile anesthetic agent such as Sevoflurane could be beneficial in the treatment and prevention of this respiratory condition. By improving gas exchange and attenuating pulmonary inflammation in particular, this agent would make it possible to prevent deterioration or to restore pulmonary function more rapidly. Half of the patients will receive inhaled sedation with sevoflurane and the other half will receive intravenous sedation already routinely used in participating ICUs (typically propofol, dexmedetomidine or a benzodiazepine, i.e. drugs approved for sedation). The aim of this study is to assess whether the use of Sevoflurane could be beneficial in the prevention of ARDS.


Eligibility

Min Age: 18 Years

Inclusion Criteria5

  • Age ≥ 18 years
  • Admitted to participating ICUs with at least one known risk factor for ARDS and a LIPS equals to, or greater than, 4 (Appendix D)105
  • Patient under invasive mechanical ventilation
  • With expected duration of sedation superior or equal to 4 hours
  • Affiliation to the French Sécurité Sociale

Exclusion Criteria16

  • Patient under judicial protection, guardianship or supervision, as defined by art L1121-8 of the Public Health Code
  • Patient under psychiatric care as defined by art. L1121-6 of the Public Health Code
  • Patient deprived of their freedom by judiciary or administrative order
  • Known pregnancy
  • Presence of ARDS prior to randomization
  • Endotracheal ventilation for greater than 24 hours prior to randomization
  • Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
  • Tidal volume of 6 mL/kg predicted body weight (PBW) below 200 mL (i.e. height inferior to 134cm for a man and 139cm for a woman)
  • Moribund patient, i.e. not expected to survive 24 hours despite intensive care
  • Previous hypersensitivity or anaphylactic reaction to sevoflurane or to the intravenous sedation agent routinely used in the participating ICU (such as midazolam, propofol, or dexmedetomidine)
  • Absolute contra-indications to the intravenous sedation agent routinely used in the participating ICU (such as midazolam, propofol, or dexmedetomidine)
  • Medical history of malignant hyperthermia
  • Long QT syndrome at risk of arrhythmic events
  • Medical history of liver disease attributed to previous exposure to a halogenated agent (including sevoflurane)
  • Suspected or proven intracranial hypertension
  • Enrollment in another interventional trial with direct impact on oxygenation

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Interventions

DRUGInhaled sedation with sevoflurane

In both arms, the management of sedation will be conducted in the broader picture of ICU patient care, as per current standard practice in participating ICUs, and following the current guidelines for Pain, Agitation, Delirium, Immobility, and Sleep Disruption (PADIS) published in 2018 by the Society of Critical Care Medicine. Among many recommendations, this will include the monitoring and titration of both sedation and analgesia using validated scores such as the Richmond Agitation-Sedation Scale (RASS) for sedation. As a result of the current recommendations, the level, dose, and duration of sedation will vary among patients and will be decided by the treating clinicians. The choice of the analgesic drug(s) will be as per the treating clinicians. Other aspects of critical care will adhere to standard care, including the use of the "Checklist for Lung Injury Prevention" (CLIP).

DRUGIntravenous sedation (current practice)

In both arms, the management of sedation will be conducted in the broader picture of ICU patient care, as per current standard practice in participating ICUs, and following the current guidelines for Pain, Agitation, Delirium, Immobility, and Sleep Disruption (PADIS) published in 2018 by the Society of Critical Care Medicine. Among many recommendations, this will include the monitoring and titration of both sedation and analgesia using validated scores such as the Richmond Agitation-Sedation Scale (RASS) for sedation. As a result of the current recommendations, the level, dose, and duration of sedation will vary among patients and will be decided by the treating clinicians. The choice of the analgesic drug(s) will be as per the treating clinicians. Other aspects of critical care will adhere to standard care, including the use of the "Checklist for Lung Injury Prevention" (CLIP).


Locations(1)

CHU Clermont-Ferrand

Clermont-Ferrand, Not Required For This Country, France

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NCT05849779


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